Nervous system disorders affect millions of people, sometimes causing death or degradation of life. Central and peripheral nervous system disorders include epilepsy, Parkinson's disease, essential tremor, dystonia, and multiple sclerosis (MS). Other nervous system disorders include mental health and psychiatric disorders, which also affect millions of individuals and include anxiety (such as general anxiety disorder, panic disorder, phobias, post traumatic stress disorder (PTSD), and obsessive compulsive disorder (OCD)), mood disorders (such as major depression, bipolar depression, and dysthymic disorder), sleep disorders (narcolepsy), obesity and anorexia.
Epilepsy is the most prevalent serious neurological disease across all ages. Epilepsy is a group of neurological conditions in which a person has or is predisposed to recurrent seizures. A seizure is a clinical manifestation of neurological activity indicative of a nervous system disorder, and results from excessive, hypersynchronous, abnormal electrical or neuronal activity in the brain. This electrical excitability of the brain may be likened to an intermittent electrical overload that manifests with sudden, recurrent and transient changes of mental function, sensations, perceptions and/or involuntary body movement. Because seizures are unpredictable, epilepsy affects a person's employability, psychosocial life and ability to perform otherwise standard tasks such as operating vehicles or heavy equipment.
Over time seizure repetition may result in neuronal cell loss at or near the seizure focus (such as with hippocampal sclerosis) and the neuronal network involved in seizure propagation. If the cell loss is significant, the firing patterns of the neural network may change, becoming less complex and/or chaotic. Such loss of irregularity in neuronal network firing patterns has been postulated to give rise to seizures.
Treatment therapies for epilepsy and other nervous system disorders can include any number of possible modalities alone or in combination including, for example, electrical stimulation, magnetic stimulation, drug infusion, and/or brain temperature control.
Devices and methods to therapeutically stimulate the body, e.g., the human body, are well known in the art. Some of these devices and methods vary, at least to some degree, the electrical stimulation provided.
Some devices and methods have multiple stimulation sites and modification which stimulation sites are activated at any given time. For example, U.S. Pat. No. 4,390,023, Rise, Patterned Electrical Tissue Stimulator, Medtronic, Inc., discloses a patterned electrical tissue stimulator includes a current source and analog multiplexers connected to an array of electrodes attached to the body. Microprocessor control of the multiplexer and the current source provides automatic selection of electrode stimulation pairs whereby spatial patterns of electrical stimulation are produced. Temporal summation and temporal patterns of electrical stimulus are provided through microprocessor control of the current source.
Also U.S. Pat. No. 4,556,064, Pomeranz et al, Electrotherapy Acupuncture Apparatus and Method, and European Publication No. EPO160753A1, European Application No. 84302741, Pomeranz et al, Electrotherapy Acupuncture Apparatus and Method, International Medical Machines, Inc., published Nov. 13, 1985, disclose a circuit for electrotherapy and electronic acupuncture, in which a pulse train is produced having negative pulses of a repetition rate of between 100 and 500 Hertz, arranged in groups having a repetition rate of between 1 and 50 Hertz. A positive bias is provided so that the integral of the pulse train signal is zero. The signal is randomly switched sequentially from one skin stimulus site to another with application times which can be adjusted between about 1 and 20 seconds (or more), to reduce or prevent brain habituation. Optionally there is a rest period between applications of the signal, in which no signal is applied to the skin sites.
Other devices and methods make at least one parameter of an electrical stimulation signal a function of another parameter. U.S. Pat. No. 4,887,603, Morawetz et al, Medical Stimulator With Stimulation Signal Characteristics Modulated as a Function of Stimulation Signal Frequency, Empi, Inc., and U.S. Pat. No. 4,922,908, Morawetz et al, Medical Stimulator With Stimulation Signal Characteristics Modulated as a Function of Stimulation Signal Frequency, Empi, Inc., disclose transcutaneous electrical nerve stimulation (TENS) apparatus which include first, second, and third oscillators. The first oscillator produces a first train of pulses at a main frequency. The second oscillator produces a second train of pulses at a modulation frequency. Output levels of the second train of pulses vary as a function of the modulation frequency. A frequency control simultaneously controls both the main and modulation frequencies. The third oscillator is responsive to the first and second oscillators and produces a third train of pulses at the main frequency. Intensity and frequency of the pulses of the third pulse train are modulated as a function of the output levels of the second train of pulses. An output driver responsive to the third oscillator converts the third train of pulses into a train of stimulation pulses having electrical characteristics adapted to be applied to a human body to suppress pain.
In another apparatus, electrical stimulation of the carotid sinus nerve is based upon a detected biological condition. U.S. Pat. No. 3,650,277, Sjostrand et al, Apparatus For Influencing the Systemic Blood Pressure in a Patient By Carotid Sinus Nerve Stimulation, LKB Medical AB, discloses a system for reducing and controlling the blood pressure of a hypertensive patient has electrical pulse stimulation of the carotid sinus nerves controlled by the arterial blood pressure of the patient in such a manner that the number of stimulation pulses within each heart cycle is determined by the arterial means blood pressure whereas the distribution of stimulation pulses over the heart cycle is a function of the arterial pulse wave shape with the pulse frequency being greater during the first portion of the heart cycle.
In still other devices and methods, electrical stimulation provided is varied according to predetermined criteria. U.S. Pat. No. 3,954,111, Sato, Electric Therapeutical Apparatus With Audio Frequency Band Alternating Current, discloses an electric therapeutic method and apparatus for medically treating diseases caused in the human body by utilizing natural phenomena that organisms including human being endowed with natural curative properties, that alternating current (generally referred to as biological electric current) is found in live cells and that the more active the vital action in cells, the more intensive biological current flows therein, through the introduction of alternating current into affected cells having abnormalities in their functions to activate the vital actions thereof, thereby enhancing the natural curative properties which such cells are originally endowed with. Also, U.S. Pat. No. 3,983,881, Wickham, Muscle Stimulator, Telectronics Pty., published Oct. 5, 1976, discloses an improved muscle stimulator, particularly suited to long term rhythmic stimulation for the selective development of musculature otherwise asymmetric or retarded in relative development. To minimize the subjects' awareness of stimulation, to permit nocturnal use, and to minimize battery consumption, the energy content of each pulse train is modulated by a progressive increase of pulse width up to a maximum, followed by a progressive decrease of pulse width, thus yielding a gradual contraction and relaxation of the muscle. U.S. Pat. No. 4,210,151, Keller, Jr., Electronic Pain Control With Scanned Output Parameters, Stimtech, Inc., discloses a device in which a first oscillator. dictates the pulse duration and frequency of stimulating signals; the oscillator output wave form is coupled to an output amplifier stage, and thence to the patient. A scanning oscillator provides a substantially linear ramp voltage, which in turn controls pulse duration, pulse frequency, and pulse intensity modulators. In turn, these modulators appropriately establish conditions within the first oscillator and the output stage whereby the output parameters are scanned through respective predetermined ranges, thereby periodically achieving optimum stimulating conditions.
Electrical stimulation may be determined by a predetermined formula. U.S. Pat. No. 5,755,749, Sakano, Change Control Method Using Three-Dimensional 1/F Fluctuation, Recording Medium Storing the Method, and Change Control Device Using Three-Dimensional 1/F Fluctuation, Toyo Sangyo Co., discloses a method for controlling changes in stimulation of every sort and kind including electrical stimulation, utilizes a three-dimensional 1/f fluctuation. The method is a change control method for controlling changes in stimulation to an object using a three-dimensional 1/f fluctuation and includes the steps of causing changes based upon 1/f fluctuation periods in the X-Z plane of a X-Y-Z space, causing changes based upon 1/f fluctuation periods in the X-Y plane of the space, superposing the caused changes of the previous steps, and applying the superposed caused changes to the object. This makes it possible to realize a low-frequency device free of problems attributable to the tolerance in neural response. A recording medium used to store the change control method, and a change control device using a three-dimensional 1/f fluctuation are also disclosed. Changes based on 1/f fluctuation periods in the X-Z plane and changes based on 1/f fluctuation periods in the X-Y plane are superposed on each other. In the case where stimulation is changed so as to avoid monotonous application of stimulation, for example, in a massaging device, it is possible to perform control for providing three-dimensional changes in the stimulation in which changes occur in both the vertical and horizontal directions, in addition to changes in the stimulation based on two-dimensional 1/f fluctuation periods at a single stimulation point. Thus, it becomes possible to effect control for stimulation changes which are natural and comfortable to an extent that they are closely correspond to the human physiology.
Still other devices and methods provide varied electrical stimulation in a variety of ways.
UK Published Patent Application No. 2 163 355A, Simonin, A Device For Aesthetic Skin Treatment, published Feb. 26, 1986, discloses a device for the aesthetic treatment of the skin and which essentially comprises a pulse generator, of which the positive and negative outputs are each connected to a plurality of fine solid skin penetrating needles which are fitted to the ends of respective flexible connecting wires. The device is applicable in particular to the treatment of the wrinkles of the skin of an individual. The needles are inserted into individual sockets inside insulating shrouds.
United States Published Patent Application No. 2002/0055762A1, Gliner, System and Method for Varying Characteristics of Electrical Therapy, U.S. Ser. No. 09/751,503, published May 9, 2002, discloses a system and method for providing percutaneous electrical nerve stimulation therapy to a patient. A method in accordance with one embodiment to the invention can include coupling an electrode to the recipient, applying electrical pulses to the probe, and varying a characteristic of the pulses applied to the recipient. For example, the pulses can be automatically varied from a value of no more than about 4 Hertz to a value of no less than about 10 Hertz and back over a period of greater than 6 seconds. The frequency variation can be repeated for a number of periods during the course of a session, or the frequency characteristics can change with subsequent periods. Characteristics of the electrical pulses can be changed depending on the duration of the session. The method for varying characteristics of the electrical pulses can be automatically implemented by a computer.
PCT Patent Application No. WO 02/30509A2, Gliner, System and Method For Varying Characteristics of Electrical Therapy, Vertis Neuroscience, discloses a system and method for providing electrical nerve stimulation therapy to a recipient. A system in accordance with one embodiment to the invention can include electrode means (such as a percutaneous electrode) coupleable to a recipient. The system can further included signal generating means for applying an electrical signal to the electrode means. The signal generating means can include frequency varying means for applying the electrical signal to the electrode means at a plurality of frequencies.
U.S. Pat. No. 2,350,797, Morland et al, Means For Producing Electric Impulses, discloses an apparatus for treatment of nerves and muscles by means of electric impulses, especially for artificial innervation of muscles, for instance for therapeutic purposes. The apparatus according to the invention is especially adapted for use in the training of muscles.
U.S. Pat. No. 4,121,594, Miller et al, Transcutaneous Electrical Nerve Stimulator, Med General, Inc., discloses a transcutaneous electrical nerve stimulator in which a unijunction transistor relaxation oscillator is used to produce variable frequency, variable width pulses. The relaxation oscillator drives a two stage transistor amplifier and the output therefrom is transformer coupled to a set of output electrodes which are adapted to be placed on the area of a patient to be treated. The amplitude of the signals applied to the patient as well as the rate and duration thereof are controllable so that the patient may adjust the nerve stimulation to suit his particular needs.
U.S. Pat. No. 4,153,059, Fravel et al, Urinary Incontinence Stimulator System, Minnesota Mining and Manufacturing Company, discloses a urinary incontinence stimulator system using an intra-anal electrode which provides a recurring series of pulses of varying duration and frequency to the electrode with each of such series of pulses spaced from the succeeding series by a rest period when no pulses are provided to the electrode.
U.S. Pat. No. 5,069,211, Bartelt et al, Microprocessor Controlled Electronic Stimulating Device Having Biphasic Pulse Output, Staodyn, Inc., discloses an electronic stimulating device is disclosed, with the stimulating device particularly illustrated being a transcutaneous nerve stimulating (TENS) device for effecting suppression of pain by nerve fiber stimulation. Biphasic constant current output pulses are applied to a user through electrode pairs non-invasively positioned at the skin of the user. Microprocessor generated control pulses control generation of the biphasic output pulses at a biphasic output stage associated with each electrode pair, and the generated biphasic output pulses are capacitively coupled from each output stage which also includes a bleeder network for effecting capacitor discharge. Stimulation may be continuously applied at a level selected by the user or may be applied in timed varying intensities the maximum level of which is selectable, and displays of intensity and sensed faults, including low battery voltage, are also provided.
U.S. Pat. No. 5,269,304, Matthews, Electro-Therapy Apparatus, and British Patent No. 2255719A, Matthews, Electro-Therapy Apparatus, published Nov. 11, 1992, disclose an electro-therapy apparatus includes at least two electrodes adapted to feed oscillating current to selected sites on or beneath the epidermal or mucous surface remote from a treatment site. A common return electrode is provided at the treatment site which is subjected to the sum of the currents from the two feed electrodes. The feed electrodes may be contact feed electrodes or capacitative feed electrodes. The feed electrodes may operate at different frequencies so that the treatment site is stimulated by the beat frequency. This may be at or about 80 or 130 Hertz, if an anaesthetizing effect is required.
Still further, some devices and methods use a random or pseudo-random variation of electrical stimulation parameters.
U.S. Pat. No. 4,338,945, Kosugi et al, Method and Randomized Electrical Stimulation System For Pain Relief, Clinical Engineering Laboratory, discloses a system for generating electrical pulses for relieving the pain of the patient comprising a pulse generator and a controller for modulating the parameters of the output pulses of the pulse generator to fluctuate in accordance with the 1/f rule; i.e., the spectral density of the fluctuation varies inversely with the frequency.
U.S. Pat. No. 3,489,152, Barbara, Electrotherapeutic Apparatus With Body Impedance Sensitive Intensity Regulation, discloses an electrotherapeutic device embodying means for generating random, infrasonic and other varying signals, and applying the amplified signals to the human body for diagnostic and therapeutic purposes. The intensity of the applied signals is controlled by means responsive to changes in the impedance of the patient's body.
U.S. Pat. No. 4,431,000, Butler et al, Transcutaneous Nerve Stimulator With Pseudorandom Pulse Generator, Gatron Corporation, discloses an aphasias and other neurologically based speech and language impairments are treated by means of a transcutaneous electrical nerve stimulator. Preferably an irregular pulse train is applied by means of a pseudorandom pulse generator to the stimulator electrodes. The trapezoidal, monophasic pulses mimic typical physiological wave forms and the average pulse rate is in the order of the alpha rate. A series of pulses has a zero DC level which enables the nerves to repolarize, and a current source in the stimulator reduces the effects of such variables as skin resistance. The base pulse rate, pulse width and pulse amplitude can be adjusted to meet the particular needs of a patient.
U.S. Pat. No. 4,541,432, Moline-Negro et al, Electric Nerve Stimulator Device, Neurotronic Ltd., discloses an electric nerve stimulation device and apparatus for suppressing organic pain and other functional disorders of the nervous system without noxious sensation and substantially free from the adaptation phenomenon which usually results from subjecting receptors and nerve cells to uniform stimulating signals. The device includes a pulse generator to produce bipolar rectangular waveforms at preselected repetition rate and of a preselected width during a given first time period. Electronic circuits are connected to the post generator to deliver rectangular waveforms at a repetition rate which is chosen by a pseudo-random function for a second time period which is also chosen by a pseudo-random function. Further circuitry is provided to inhibit delivery of pulse waves for a third period of time. This third period of time is chosen by a pseudo-random function, thereby substantially eliminating noxious sensations and adaptation of nerve cells to stimulation during suppression of the organic pain. Electrodes are connected to the output of the device to apply the waveforms to nerve fibers to be stimulated thereby.
U.S. Pat. No. 5,683,422, Rise, Method and Apparatus For Treating Neurodegenerative Disorders By Electrical Brain Stimulation, Medtronic, Inc., discloses techniques for stimulating the brain to reduce the effects of neurodegenerative disorders by means of an implantable signal generator and electrode. A sensor is used to detect the symptoms resulting from the disorder. A microprocessor algorithm analyzes the output from the sensor in order to regulate the stimulation delivered to the brain.
U.S. Pat. No. 5,792,212, Weijand, Nerve Evoked Potential Measurement System Using Chaotic Sequences For Noise Rejection, Medtronic, Inc., discloses a measurement system for measuring signals evoked in response to stimulus pulses applied to a nerve, muscle or like physiological portion of a patient. The measurement system is characterized by delivering stimulus pulses at randomly generated intervals, and enabling the sense circuitry to track the timing of the stimulus pulse generation so as to aid in discriminating the evoked response pattern from surrounding noise. Specifically, after each stimulus pulse a delay is timed out for a time corresponding to the expected latency between the delivered pulse and the arrival of the evoked response at another location. The delay signal is then used to initiate time out of a window which controls operation of the sensing circuit for a window duration corresponding to when the evoked response pattern is appearing. Limiting the sensing operation to the window duration enables tracking of the response pattern, and minimizes power consumption. The sensed evoked response signals are further processed to provide control signals for adjustment of the delay and window, thereby optimizing the sensing operation. The measurement system is suitably part of a larger implantable stimulus system, which includes the ability to adjust pulse-to-pulse interval, or rate, and also pulse output level as a function of measured evoked response patterns. In a further embodiment, the stimulus system involves steering of stimulus pulses to selected nerve fibers or muscle tissue, and the measurement system provides feedback for adjusting the steering parameters.
U.S. Pat. No. 6,188,929, Giordano, Sequentially Generated Multi-Parameter Bioelectric Delivery System and Method, discloses a device and method for electro-stimulation. The user can select an overall treatment protocol of current frequencies and amplitudes to be applied for specified dwell periods defining a sweep cycle. The user can select for one or more periods in the cycle a frequency/amplitude to be applied to elicit a response such as a muscle contraction or the like. The device protocols may be selected to elicit responses while conserving power, to provide for heating without eliciting a response or to hop between frequency/amplitude combinations to produce the desired effect.
United States Published Patent Application No. 2003/0135248A1, Stypulkowski, Variation of Neural-Stimulation Parameters, U.S. Ser. No. 10/044,405, Medtronic, Inc., published Jul. 17, 2003, and PCT Published Patent Application WO 2003/059,441, Stypulkowski, Variation of Neural-Stimulation Parameters, Medtronic, Inc., disclose techniques for varying stimulus parameters used in neural stimulation to improve therapy efficacy, minimize energy consumption, minimize undesired side effects, and minimize loss of therapeutic effectiveness due to physiologic tolerance to stimulation. Neural stimulation is provided having a stimulation amplitude, a stimulation frequency, a stimulation pulse duration, an electrode-firing pattern, and a set of electrode-firing-polarity conditions. At least one of the stimulation parameters is pseudo-randomly varied. A second stimulation parameter is changed based upon having pseudo-randomly varied the first stimulation parameter and based upon a predetermined relationship specifying how changes in the first parameter affect desirable values for the second parameter.
Therapy directed to the network, which is capable of restoring complexity of network firing patterns, may be beneficial in preventing seizures. To achieve this, asynchronous electrical stimulation may be directed at the seizure focus site, or applied indirectly to nearby neurons connected via projection pathways (e.g. thalamus). The effect of asynchronous stimulation is twofold: to activate neurons that would otherwise remain silent; and, to increase the firing rate of existing neurons in the network.